Cellular models to study dopaminergic injury responses

Abstract

The study of immature midbrain dopamine (DA) neurons and dopaminergic cell lines in culture provides an opportunity to analyze mechanisms of cell death and avenues of potential intervention relevant to Parkinson's disease (PD) in a controlled environment. Use of cell culture models has provided evidence for different sets of intracellular changes associated with DA neuron death following exposure to the neurotoxins 6-hydroxydopamine and MPP+, supporting roles for oxidative stress and impaired energy metabolism as significant factors endangering these cells. Interference with death of cultured DA neurons has provided an initial test system that has yielded all the identified neurotrophic factors for DA neurons. More recent work suggests that combinations of molecules secreted by myelinating glial cells and their precursors provide even greater neuroprotection for DA neurons. Most recently, culture systems have been used to implicate microglial activation in DA neuron injury, providing impetus to the investigation of antiinflammatory agents as potential therapeutics for PD. Thus, cell culture models provide an important bidirectional link between mechanistic studies and clinically relevant observations.